the life, achievements and legacy of a great canadian ...pavlov’s exciting environment he became...

Can J Gastroenterol Vol 20 No 9 September 2006 579

The life, achievements and legacy of a great Canadianinvestigator: Professor Boris Petrovich Babkin

(1877-1950)

Ivan T Beck MD PhD FRCPC FACP MACG

Department of Medicine and Physiology, Gastrointestinal Disease Research Unit, Queen’s University, Kingston, OntarioCorrespondence and reprints: Dr Ivan T Beck, Queen’s University, Division of Gastroenterology, Hotel Dieu Hospital, Kingston,

Ontario K7L 5G2. Telephone 613-544-3310 ext 3058 or 613-544-0225, fax 613-544-3114, e-mail [email protected]

IT Beck. The life, achievements and legacy of a great Canadian

investigator: Professor Boris Petrovich Babkin (1877-1950).

Can J Gastroenterol 2006;20(9):579-588.

The present paper reviews the life and achievements of ProfessorBoris Petrovich Babkin (MD DSc LLD). History is only worthwriting about if it teaches us about the future; therefore, this histori-cal review concludes by describing what today’s and future gastroin-testinal physiologists could learn from Dr Babkin’s life.Dr Babkin was born in Russia in 1877. He graduated with an MDdegree from the Military Medical Academy in St Petersburg, Russia,in 1904. Not being attracted to clinical practice, and after some hesi-tation concerning whether he would continue in history or basic sci-ence of medicine, he entered the laboratory of Professor IvanPetrovich Pavlov. Although he maintained an interest in history, inPavlov’s exciting environment he became fully committed to physiol-ogy of the gastrointestinal system. He advanced quickly in Russia andwas Professor of Physiology at the University of Odessa. In 1922, hewas critical of the Bolshevik revolution, and after a short imprison-ment, he was ordered to leave Russia. He was invited with his familyby Professor EH Starling (the discoverer of secretin) to his departmentat University College, London, England. Two years later, he wasoffered a professorship in Canada at Dalhousie University, Halifax,Nova Scotia. After contributing there for four years, he joined McGillUniversity, Montreal, Quebec, in 1928 as Research Professor. Heremained there for the rest of his career. Between 1940 and 1941, hechaired the Department, and following retirement, he remained asResearch Professor. At the invitation of the world-famous neurosur-geon, Wilder Penfield, Dr Babkin continued as Research Fellow in theDepartment of Neurosurgery until his death in 1950 at age 73.His major achievements were related to establishing the concept ofbrain-gut-brain interaction and the influence of this on motility, aswell as on interface of multiple different cells, nerves and hormones onsecretory function. He had a major role in the rediscovery of gastrin.He established a famous school of gastrointestinal physiologists atMcGill University. He supported his trainees and helped them estab-lish their careers. He received many honors: a DSc in London,England, and an LLD from Dalhousie University. Most importantly, hewas the recipient of the Friedenwald Medal of the AmericanGastroenterological Association for lifelong contributions to the field.Dr Babkin taught us his philosophical aspect of approaching physiology,his devotion to his disciples and his overall kindness. Most importantly,he has proven that one can achieve international recognition bypublishing mainly in Canadian journals. He is an example to follow.

Key Words: Biography; Boris Petrovich Babkin; Brain-gut-brain

interaction; Friedenwald Medal; Gastrin; GI secretions; Ivan Petrovich

Pavlov; McGill University; Mentor; Physiologist

La vie, les réalisations et l’héritage d’un grandchercheur canadien, le professeur BorisPetrovich Babkin (1877-1950)

Le présent article récapitule la vie et les réalisations du professeur BorisPetrovich Babkin (MD D. Sc. LL. D.). L’histoire ne mérite d’être écriteque si elle nous informe sur l’avenir. Par conséquent, la présente analysehistorique se termine par une description de ce que les gastroentérologuesd’aujourd’hui et de demain pourront tirer de la vie du docteur Babkin.La docteur Babkin est né en Russie en 1877. Diplômé en médecine de l’a-cadémie médicale militaire de St. Petersburg, en Russie, en 1904, il n’étaitpas attiré par la pratique clinique et, après quelques hésitations entre l’his-toire de la médecine et les sciences fondamentales, il est entré au labora-toire du professeur Ivan Petrovich Pavlov. Bien qu’il ait conservé unintérêt pour l’histoire, dans le milieu captivant de Pavlov, il est devenupassionné de physiologie du système gastro-intestinal. Il a évolué rapide-ment en Russie et est devenu professeur à l’université d’Odessa. En 1922,il a critiqué la révolution bolchévique et, après un bref emprisonnement,on lui a ordonné de quitter la Russie. Avec sa famille, il a été invité par leprofesseur EH Starling (le découvreur de la sécrétine) à son départementde l’University College de Londres, en Angleterre. Deux ans plus tard, onlui a offert un titulariat au Canada, à l’université Dalhousie de Halifax, enNouvelle-Écosse. Après quatre ans à cette université, il est arrivé àl’Université McGill de Montréal, au Québec, en 1928, à titre de pro-fesseur de recherche. Il y est demeuré jusqu’à la fin de sa carrière. Entre1940 et 1941, il a présidé le département et, après sa retraite, il a poursuivises activités de professeur de recherche. À l’invitation de Wilder Penfield,neurochirurgien de renommée internationale, le docteur Babkin estdevenu chercheur au département de neurochirurgie, où il est restéjusqu’à son décès en 1950, à l’âge de 73 ans.Ses principales réalisations sont reliées à l’adoption du concept d’interac-tion cerveau-tractus digestif-cerveau et à l’influence de ce concept sur lamotilité et sur l’interface de multiples cellules, nerfs et hormones avec lafonction sécrétoire. Il a joué un rôle prépondérant dans la redécouverte dela gastrine. Il a fondé une célèbre école de physiologues gastro-intestinauxà l’Université McGill. Il a soutenu ses stagiaires et les a aidés à asseoir leurcarrière. Il a reçu de nombreux hommages : un D. Sc. à Londres, enAngleterre, et un LL. D. de l’université Dalhousie. De plus, il est lauréatde la médaille Friedenwald de l’American Gastroenterological Associationpour son apport d’une vie à ce champ de compétences.Le docteur Babkin nous a enseigné son abord philosophique de la phy-siologie, son dévouement envers ses disciples et sa gentillesse en tout. Par-dessus tout, il a démontré qu’il est possible d’obtenir une reconnaissanceinternationale en publiant surtout dans des journaux canadiens. C’est unexemple à suivre.

HISTORICAL REVIEW

©2006 Pulsus Group Inc. All rights reserved

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In response to a request by Dr Paul Adams, Editor-in-Chief ofThe Canadian Journal of Gastroenterology, to prepare ahistorical review on Dr Babkin, I undertook this task withpleasure, remembering that on my arrival to Canada, Dr Babkin was responsible for helping to provide my first job inCanadian science. Soon after I arrived in Montreal, Quebec,in 1949, I met Dr Babkin based on a letter by my previousmentor, Dr Edouard Frommel, Professor of Pharmacology inGeneva, Switzerland, who knew Dr Babkin well (1); at thattime, they were both researching the effect of quinine andatabrine on the autonomic nervous system (2-6), and my thesiswas also on this subject (7). Based on this common interestand after a personal encounter, Dr Babkin was instrumental inarranging for my first appointment in Canada as Lecturer ofPharmacology at McGill University, Montreal, Quebec.Unfortunately, our acquaintance was short lived, because hedied in 1950, one year after I met him.

When I met Dr Babkin in 1949, he had retired from his postof Head of the Department of Physiology (Figure 1), butremained Research Professor of Physiology. At the invitationof the world-renowned neurosurgeon, Dr Wilder Penfield, heworked as ‘Fellow of the University’ and Research Fellow atthe McGill Department of Neurology and Neurosurgery. Atthat time, I did not realize that it was during this period that hedid one of his most pioneering works – localizing gastrointesti-nal (GI) function in the brain (8-12). As a young, immigrantphysician, I had little knowledge of the grandeur and loneli-ness of this recently found friend who treated my wife and mewith warmth, and showed deep understanding of the difficul-ties that a recent immigrant physician may have encountered.When we met him, although many of his colleagues admiredhim, he appeared to be a very lonely man. Later I discoveredthat he lost his wife, the well-known histologist Dr HeleneSoloviev, 10 years before in 1939, his eldest daughter as a resultof the Russian Revolution and his younger daughter (the bal-let dancer Xenia Kernan) in 1944 (13,14). He lived alone inone of the rooms reserved for senior faculty at the very austereand impressive Faculty Club of McGill. My wife and I wereinvited on several occasions to the Club, which, at that time,did not admit lecturers or women in the general reading room.Because of my wife, we had to eat in a dining room in whichwomen were permitted to enter. We immediately felt what waslater stated by Carlson (15): “By his sympathy and assistance toothers, Dr Babkin proved himself a true humanitarian”, andbased on “his inherent kindness and sympathetic understand-ing” (15), he helped many newcomers, including myself. Mostimportantly, when we started to discuss research, his eyes litup, and he shared his enthusiasm and love with me, as withmany of his disciples, for the ongoing new developments andapproaches to the physiology of the digestive tract. It is duringthese discussions that I decided that my future line of researchwould be in gastroenterology.

Having known him for only a short time, what follows, inaddition to my own reading of his work, has been obtainedfrom several obituaries regarding his life and achievements(13-16), and by browsing the archives of the Osler Library atMcGill .

Dr Babkin’s work demonstrates a complete circle ofunderstanding of the effect of the nervous system on the gut. Inhis youth, he studied the effect of nerves on the GI tract (17)and during his last years of investigation, he focused on thecerebral localization of GI function (8-12). Dr Babkin’s workremains the basis of the recently rediscovered brain-gut-brain

interaction. His interests ranged widely. He made majorcontributions in several other fields, specifically in GI motility;he established the presently still accepted basic aspects ofmechanisms of secretions; also, he had a major role in therediscovery of gastrin.

BABKIN’S LIFE HISTORYBabkin’s early achievements in RussiaDr Babkin, the son of an army officer, was born in 1987 inKursk, Russia. He finished high school in St Petersburg andentered the Military Medical Academy (St Petersburg) in1898. During his third year of study, he saw in the Academyvestibule an announcement for a gold medal for the best essayon one of several subjects, one being “The influence of artifi-cial sutures of the skull on its growth and development inyoung animals”. This theme was based on a suggestion by aFrench surgeon, Dr Lannelongue, that opening of the suturesof microcephalics may provide freedom to develop normally.Babkin approached Dr Bechterev for supervision. In this labo-ratory, however, there was little supervision or help fromDr Bechterev, and Babkin’s work was not corrected or dis-cussed. It was submitted as such to the Academy. Although hereceived the medal and the unsupervised work was publishedin a Russian neurological journal, it left him worried of its pos-sible inaccuracy. He did not have time to reinvestigate it until1942 and 1943 with the help of Professor Norris Giblin andMiss Armine Alley at McGill, and he found that his young,inexperienced findings were in fact correct (see pages 74-77 in

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Can J Gastroenterol Vol 20 No 9 September 2006580

Figure 1) Portrait of Professor Boris Petrovich Babkin. This paintingis hanging in the Department of Physiology, McGill University,Montreal, Quebec, commemorating Dr Babkin as a scientist and Headof the department between 1940 and 1941. Permission to use thisphotograph was provided by Dr Alvin Shrier, Chair of the department

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Babkin’s biography of Pavlov [18]). Having finished medicalschool, he had little interest in clinical medicine, and intendedto combine studies in the history of medicine with work in theresearch laboratory. In January 1902, he approached ProfessorIvan Petrovich Pavlov, Chair of Physiology at the Institute ofExperimental Medicine in St Petersberg, to join his laboratory.Dr Babkin became an outstanding disciple of Professor Pavlovand continued in the same field. He joined this laboratoryunsure of whether his main interest was history of medicine orscientific work. Although his fascination with history andmusic was maintained throughout his life, under ProfessorPavlov’s tutorship his main commitment became science (14).

In 1902, Pavlov set him up to study the influence of soapson the secretion of the pancreas. The results were reported atthe Congress of Northern Naturalists and Physicians inHelsingfors in 1902 and were published in the proceedings ofthe Congress (referenced in 14). He was an assistant to Pavlovat the time when Pavlov began to change from work ondigestion alone to the problem of conditioned reflexes. Based

on this experience, Dr Babkin, throughout his scientific life,continued to combine studies of the effects of the nervoussystem on GI function. Many of his early papers were publishedin Russian, which few Europeans or Americans could read. Hisfirst major papers in German were published in Pflügers Archive(19,20). In these studies (in which, in the fashion of earlyphysiologists, he described each experiment separately), heestablished that discharges from the salivary gland werestimulated by parasympathetic and not sympathetic nerves(19,20). Figures 2A and 2B demonstrate the care with whichhe organized and described each experiment. His findingscontradicted the established Heidenhein’s theory of ‘secretory’and ‘trophic’ nerves. This created controversy and thusexposure outside of Russia. Next, his monograph “Die äussereSekretion der Verdaungsdrüsen” (“External secretion ofdigestive glands”) was published in German in 1914 bySpringer in Berlin, Germany ([21] quoted by [14]), providinghim an even wider audience.

Immigration and early times in the westBetween 1915 and 1922, Dr Babkin was Professor ofPhysiology at the University of Odessa, Ukraine. Here, hismain work was on glandular secretion, intestinal motility, theirchemical stimulation and the correlation of the two. Becauseof his liberal attitude, he was upset by brutalities of the Russianrevolution. In 1922, he was denounced to the authorities asdisloyal and was thrown in prison in Odessa. Ten days later, hewas exiled from Russia. By then, his monograph on theexternal secretions of digestive glands (21), which had beenpublished in German, gave him international reputation to beinvited with his family by Professor EH Starling to his depart-ment at University College, London, England. Here, heworked in a world-renowned environment. Starling andBayliss (22) discovered secretin and established the concept ofendocrinology (22-24). In this laboratory, Dr Babkinflourished and became interested in the interaction of nerves,chemical transmission and endocrine secretions (25). Hedescribed, with Starling, a new method of perfusing the pan-creas (26). Figure 3 indicates the complexity and detail with

Professor Boris Petrovich Babkin: A biography


Figure 2) Increased blood flow in response to secretions of the submaxil-laris gland of the dog. The detailed description indicates the care and detailwith which Dr Babkin reported physiological experiments. Secretions werestimulated by placing meat extract in saline solution in the mouth of the dogto stimulate secretory flow. Resultant changes in blood flow were measuredby a canula inserted in the isolated vein draining blood from the gland.Depending on the anatomical structure of the venous supply, each dog hadto be prepared in a slightly different fashion. A Babkin’s drawing of exper-iment on November 26, 1911. A Vena jugularis externa; B Vena maxil-laris interna; C Vena maxillaris externa; D Vena auricularis magna; a, b,c and d are ligatures. All blood flow from the gland entered through F andE to the Vena axillaris interna, which was canulated to measure the flow.B Drawing of experiment of December 13, 1911. A Vena jugularisexterna; B Vena maxillaris interna; C Vena maxillaris externa; D Venaauricularis magna; a, b, c and d are ligatures. Because of slightly differentvascular anatomy, blood flow still went from the gland through F and E tothe ligated section of the intubated section of Vena axillaris interna.Reprinted with permission from Springer Science and Business Media,Heidelberg, Germany: Babkin BP. Secretorische und vasomotorischeerscheinungen in der speicheldrusen. Pflugers Arch Gesamte PhysiolMenschen Tiere 1913;149:497-520

Figure 3) Schematic demonstration of experimental preparation of isolatedpancreas. Note the detail of the drawing. This preparation was used byBabkin in several later experiments. Reprinted with permission fromBlackwell Publishing, 9600 Garsington Road, Oxford, Great Britain:Babkin BP, Starling EH. A method for the study of the perfused pancreas.J Physiol 1926;61:245-7

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which Babkin described his experiments, and reflects howknowledge was disseminated during the early 20th century.

It was quickly recognized what a loss he was to Russia, andseveral invitations came from there – one of them from Pavlov,who, at that time, retired; he was offered his own Chair at theMilitary Medical Academy. Dr Babkin declined, and wishingto come to North America, he accepted an invitation asinstructor from the Washington University in St Louis(Missouri, USA). Canada quickly recognized his value, and assoon as he reached the American continent, DalhousieUniversity, Halifax, Nova Scotia, offered him the position ofChair of Physiology. He arrived in Halifax in the summer of1924. There, he regained his dignity and undertook withenthusiasm his responsibility of Professorship in Physiology.He had major difficulties with the English language. His lan-guage difficulty and foreign accent made him anxious that hismedical students would not understand him. “While the lattercircumstance did occur in numerous instances, the personalityand great ability of the man compensated and impressed hisstudents in an indelible manner” (14). In his early years, hewrote his lectures in Russian and had his manuscripts correctedfor grammatical error (14). His first paper from Halifax was onchemical stimulation of GI motility, published in the CanadianMedical Association Journal (27).This article reviewed the workof many investigators in intestinal motility and provided 63 references, many of his own work. It updated the Englishliterature on studies by Russian investigators previously neverpublished in English. Reading it today, one cannot help but beimpressed that he knew all the principles of GI motility weknow today, and all we have added since are details. In this

paper, Babkin also established two principles that he carriedthrough all his life: providing a link between English andRussian investigators and publishing much of his work inCanadian journals. We can learn from him that one canreceive the highest international honors by publishing mainlyin Canadian journals.

Research at McGill UniversityAfter four years in Halifax, in 1928, he accepted the post ofResearch Professor of Physiology at McGill University, wherehe worked until his death. He chaired the Departmentbetween 1940 and 1941, and after retirement, he continued ina research position. It is at McGill that he could materialize hisbroad interest in various aspects of GI physiology. He reinves-tigated the innervations of the salivary glands and demonstratedthat stimulation of chorda tympany in the presence ofphysostigmin releases a substance that can be transferred fromone gland to the other (28). In a complex set of experiments incats, he connected the venous outflow of one submaxillarygland to that of the other. By opening and closing theconnection, he demonstrated that stimulation of chordatympani on one side released a substance that stimulated secre-tion by the gland of the other side (Figure 4A, 4B and 4C).The transmitted substance was later found to be acetylcholine,but Babkin’s observation occurred one year before Feldberg andKrayer (29) identified acetylcholine as the parasympathetictransmitter in 1933. With his ongoing studies, Babkin devel-oped a concept of the autonomic nervous system that becamethe standard of knowledge of his time. In his presidentialaddress to the Royal Society of Canada, by 1946 (in the

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Figure 4) Secretory stimulatory substance released in response to chorda tympani stimulation. Demonstration of transmission of this substance fromone salivary gland to the one on the other side. Complex surgical preparation allowed blood flow of one gland to perfuse the other. Kymographs wereused to demonstrate the event. A Kymograph of the Department of Physiology, McGill University, Montreal, Quebec. The picture was obtained fromthe department. Ms Jay Bhat kindly arranged to have this exhibit rephotographed for the present publication. This equipment may have been used byBoris Babkin. B Schematic representation of kymographic technique. Kymographs were the recording techniques available to record analogue physio-logical events before World War II. Electronic recorders were developed during the war. They became available in the early 1950s for science.Kymographs carried touch-sensitive, charcoal-coated paper, which was prepared by holding it over fumes of burning benzene. The paper moved at pre-set speeds. Styluses traced continuous records. The recording stylus could be connected to various events: blood pressure, respiration, drop count,action potentials, electrical stimulation records, etc. The imaginary experiment on this figure started at the white arrow and the drum slowly movedaway from the styli (grey arrow). The investigator rapidly took note of events on the paper as it moved (see writing at top). After each experiment, thetracing had to be carefully removed and rapidly fixed. This took two people. After cutting the paper, which was approximately 3 m long, one held it uphigh and the second placed it in a container of shellac and pulled it slowly through until the material was fully fixed in shellac. One of the most impor-tant functions of a research technician, or graduate student was to successfully prepare the paper and fix it without smearing the data. Appropriate sec-tions were then used to publish analogue data. C Tracing demonstrates the transmission of the chorda tympany effect to the submaxillary gland on theother side. Upper tracing: Salivary flow of the right submaxillary gland. The excretory duct was canulated and drops of saliva fell on the indicator. Eachdownward line indicated a drop of saliva. The rate is indicated by the frequency of the drop count. Note that stimulation of the left chorda tympanireleased a substance that perfused into the right gland, initiating salivary flow. Middle tracing: Downward deflection records of electrical stimulation,first of the right, and the second and third of the left, chorda tympani. Note that stimulation of the left nerve resulted in increased salivary flow of theright gland. Lowest tracing: Indicates time by 6 s. The writing is that of one of the authors done before finally fixing the tracing. Reprinted with per-mission from the Royal Society of Canada: The Academies of Arts, Humanities and Sciences of Canada, Ottawa, Ontario: Babkin BP, Alley A,Stavraky GW. Humoral transmission of chorda tympany effect. Trans R Soc Can 1932;26:89-107

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bibliography he gives credit to many of his disciples), he hadan astonishingly clear picture of the antagonistic and synergis-tic phenomena of the transmitters (30).

Babkin’s studies of the stomach dealt with correlating anddifferentiating nervous and chemical phases of secretions. Hewas the first to describe that acetylcholine, histamine andgastrin induce different compositions of gastric juice and thatthe composition depended on the type of cell (parietal, chief ormucus) being stimulated. He proposed (Figure 5) that hista-mine was released by acetylcholine and was secondary to vagalstimulation (31). Up until recently, contrary to Babkin’sconcept, the opinion was generally accepted that there wasequal stimulatory and possibly synergistic effects of acetyl-choline, gastrin and histamine on the parietal cell (32). Onlyin 1996 was Babkin’s theory confirmed by demonstrating thatthe vagus stimulates the neuroendocrine enterochromaffin-like cells to release histamine, which then stimulates acidsecretion of the parietal cell (33,34). In the same paper, Babkinsuggested that sympathin was not the only inhibitor of secre-tion, a concept that was later accepted and described as ‘nona-drenergic noncholinergic inhibitor’, which after manytransitions, today, may be nitrous oxide (Figure 5).

With his students, Babkin described the effect of histamineon gastric parietal, mucoid and peptic cells, and compared theaction of histamine with nervous stimulation (35). They stud-ied the use of histamine on gastric secretory activity (36) and,with DR Webster, demonstrated that insulin, by causing hypo-glycemia, stimulates central vagal nuclei. In contrast tohistamine, which stimulates parietal cells, insulin-stimulatedsecretion can be abolished with vagotomy and by atropine. Dr Babkin was asked to write an editorial on the usefulness ofthe histamine versus insulin stimulation to differentiatebetween vagally stimulated (insulin) and parietal mass (hista-mine effect) secretions (37). At the time, peptic ulcer wastreated with vagotomy, antrectomy and pyloroplasty, and it wasnecessary to know whether a recurrent ulcer was due toinadequate vagotomy or insufficient resection of the gastrincontaining antrum. His concepts of basic gastric research werean attempt to correlate physiological findings to proposedsurgical therapy (38).

After describing the effect of soaps on pancreatic functionwhile still in Pavlov’s laboratory, at McGill, he and hisstudents investigated the effects of different agents on pancre-atic secretions. They found that similar to the salivary glandsand the stomach, the compositions of pancreatic secretadiffered depending on the stimulus (39) and on the presence ofsubstances in the circulation (40). Based on studies onmultiple secretory organs, Dr Babkin established that indiverse organs, various stimuli caused different composition ofsecretion, each coming from different cell types. He proposed anew cellular theory, which is still correct, that digestive glandsconsist of compound structures in which various cells arecontrolled by different nerves or hormones (41).

BABKIN’S ROLE IN ESTABLISHING THATGASTRIN EXISTS

The story of gastrin is a tragic one. Based on the concept of thediscovery of secretin in the duodenum by Bayliss and Starling(22) in 1902, John Sydney Edkins of St Bartholomew’sHospital Medical School in London, England, suggested in1905 that a ‘gastric secretin’ (gastrin) in the antrum that mayhave been responsible for the release of gastric acid (42,43).Unfortunately, Barger and Dale (44) extracted histamine from

ergot and later from the gastric mucosa. Because Edkins’extract also caused some of histamine’s vascular effects, hisfinding was disregarded for almost 30 years. AC Ivy found thathistamine or ‘gastrin’ did not provoke gastric secretion (45).Sacks, Ivy, Burgess and Vandolah stated in 1932 that “eitherthat histamine is the gastric hormone, or if not, there is nogastric hormone, or the gastric hormone has never beenextracted from pyloric mucosa” (46). Because of the consider-able importance of these American investigators, Edkins find-ings were ridiculed by the scientific community, and it tookuntil after his death to prove that gastrin really exists. In con-trast to the general opinion, Babkin, based on his own experi-ments, continued to support the presence of gastrin, a pyloricacid stimulatory hormone. In 1934, in response to the paper bySacks et al, he described experiments in which putting food inan isolated and denervated pyloric pouch caused secretion inthe isolated fundus (Figure 6) (47). Furthermore, the composi-tion of the fundal secretions was different from that producedby histamine (48), and the pyloric stimulated secretions werenot accompanied by histamine’s vascular effect (47).

To prove that gastrin was not histamine, Babkin consideredthat only someone well trained in chemistry could separate thetwo. It was fortuitous that between 1910 and 1913, Babkin metDr Simon Andrew Komarov when they both worked inDr Pavlov’s laboratory – Babkin as an assistant and Komarov asa student. Komarov was born in Lugansk, Russia in 1892. Afterhis work at the Military Medical Academy in St Petersburg, in1915 he completed his medical education in Kharkov, Russia,obtaining an MB. He did his internship in medicine at theUniversity of Kharkov. Similarly to Babkin, Komarov found



Figure 5) Babkin’s concept of the relations of acetylcholine (AC) andhistamine (H). Note that in this scheme, the vagus releases AC, andthat this stimulates secretion of the mucus and chief cells. In contrast,the parietal cell is directly stimulated by H, which is released by ACfrom an as yet unknown site. This concept was later confirmed byshowing that AC stimulates enterochromaffin-like cells that then releasehistamine. Babkin also indicated that sympathin is not the only inhibitorysubstance. This concept was later described by others as the ‘nonadrener-gic noncholinergic’ inhibitor, and then as nitrous oxide. Reprinted withpermission from the publisher. ©1938 CMA Media Inc, Ottawa,Ontario: Babkin BP. The abnormal functioning of the gastric secretorymechanism as a possible factor in the pathogenesis of peptic ulcer. Can Med Assoc J 1938;38:421-9

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that basic science was his vocation, and, between 1916 and1922, became an assistant in biochemistry and organic chem-istry. Due to his dislike of communism, in 1922, Komarov leftRussia and immigrated to Latvia. He worked at the Universityof Riga, Latvia, as Prosecutor of Physiology between 1922 and1929. In Riga, he obtained an MD degree in 1926 (49,50). Two years after Babkin was established as a Research Professorat McGill, he invited Simon Komarov as a Research Assistantto the Department of Experimental Medicine (1930 to 1939)and, from 1939 to 1942, as a Lecturer in the Department. In1942, Komarov left McGill to be the Director of Chemistry,Medical Research Laboratory Fels Research Institute, TempleUniversity School of Medicine in Philadelphia, USA. Whileat McGill, Komarov extracted a histamine-free gastric secretorystimulant from the pyloric mucosa that increased acid, pepsinand volume secretion. It did not stimulate biliary and pancre-atic secretion and, thus, was different from secretin. It fulfilledthe criteria for a new hormone: gastrin. Komarov first presentedthis as a verbal communication (introduced by Dr Babkin) atthe Meeting of the Society of Experimental Biology andMedicine in 1938 (51). The findings presented are shown inFigure 7. Because he pursued a hypothesis that the hormone,similar to secretin, was a polypeptide, he separated it fromhistamine using methods to extract polypeptides. The work toseparate took enormous mental and physical effort, and it tooka further four years before he published the details of prepara-tion of the extract (52) and its final physiological function(53), both in the Revue canadienne de biologie.

Although the work, mainly consisting of organic chemistry,was entirely that of Komarov, it could not have been donewithout the ongoing support, patience and consideration byBabkin. One of their close coworkers, Dr Friedman, who was inthe Babkin laboratory at the time of the separation (54,55),writes in the obituary in memoriam of Komarov that, typical ofhis hard work, in some experiments he needed the collectionof up to 300 L of canine gastric juice. Can one visualize whatthis did to the general running of the unit, especially becauseKomarov may not have been easy to live with? Friedman writes(49):

“Komarov’s years at McGill were not only productive inhis research, but also in his personal life. He marriedOlga Piotrowsky … Her calm efficiency was the solventfor Simon’s sharp responses to anything that interferedwith his daily routine. It was Olga who smoothed out theproblems of every day life … She not only encouragedhim to report his many worthwhile contributions to GIphysiology, but helped him to overcome his naturalshyness”.

Komarov became, on his own, one of the world’s most out-standing physiologists while he worked in Philadelphia. Afterhis death in 1966, the American Journal of Digestive Diseasesestablished a special issue dedicated to Komarov. In this“festschrift” they collected papers from individuals affected byKomarov’s work or personal contact. In the introduction,Bralow states: “Komarov emerged as one of the world’s out-standing GI physiologists and it seems appropriate to trace thedescent of the mantle of genius from Pavlov to Babkin, toKomarov” (50 [page 76]).

BABKIN AND HIS SCHOOLIt was at McGill that Babkin established his own school andtrained many postgraduate students, many of whom soonestablished their own research excellence. A short list of hisdisciples is provided in the obituary by de Burgh Daly et al(14). In the present history, I decided to mainly use Babkin’sreviews, which were mostly published under his own name.This does not indicate that he published most of this workwithout giving credit to his students. In fact, the contrary is

Beck


Figure 7) Simon Komarov’s proof of gastrin (3). Effect on gastric, biliaryand pancreatic secretion of substances which were devoid of histamineeffect. Extracts made from the mucous membrane of fundus (F), pyloricregion (P), upper duodenum (DU) and lower duodenum (DL). Thenumbers below the letters denote the weight of mucosa equivalent to thedose of extract administered. Upper tracing: Bile flow. Middle tracing:Pancreatic flow. Lower tracing: Gastric volume and acid and pepsin secre-tion. Left markings: pepsin secretion in units, and volume in mL (cc).Right markings: acid in meq/L. Bottom markings: time in h. Note thatonly the pyloric extract stimulated gastric volume and acid and pepsinsecretion. Reprinted with permission from the Society of ExperimentalBiology and Medicine, 197 W Spring Valley Avenue, Maywood, NewJersey, USA: Komarov SA. Gastrin. Proc Soc Exp Biol Med1938;38:514-6

Figure 6) Diagram of an experiment to prove the physiological presence ofgastrin. Diagram of the gastrointestinal tract of a dog with a gastric fistula,gasroenterostomosis and an isolated pyloric pouch. Reprinted with permis-sion from Springer Science and Business Media, Heidelberg, Germany:Babkin BP. The “chemical” phase of gastric secretion and its regulation.Am J Dig Dis Nutr 1934;1:715-21

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true. The bibliography of each review provides the originalwork published by his trainees in which most are first or secondauthors in the original publication. Many became well-knowninvestigators in Canada, the United States or Europe. Of hisdisciples, several stayed at McGill. Some I knew while I was onstaff in Pharmacology and later at the Royal Victoria Hospital,Montreal, Quebec. Dr FC MacIntosh, who, when I arrived,was Professor and Head of the Department of Physiology, wasextremely helpful in my early days, the Department ofPharmacology being one floor above that of Physiology. Heand Professor Raymond Stehle, Head of Pharmacology andKenneth Melville, who worked with Babkin on atabrine (6),carried me through the same anxieties about language andaccent Boris Babkin had experienced in Halifax. Once inclinical training and then staff at the Royal Victoria Hospital,I met Dr Babkin’s clinical postgraduate students. JC Armourand DR Webster, gastric surgeons, were close friends of Dr Richard McKenna (the first president of the CanadianAssociation of Gastroenterology [56]) and were members ofour McGill gastroenterology group. Even after their postgradu-ate training (57), during World War II, when Webster wasSurgeon Commander in the Royal Canadian Navy, theycarried out studies with Dr Babkin on how to preserve thestomach after deprivation from arterial supply (58). Dr ArthurM Vineberg, another postgraduate student (35), became acardiac surgeon. He originated the concept of coronary bypasssurgery and was the first to achieve successful implants fromintercostal arteries to the heart. Both approached surgery withthe judgment expected from disciples of Babkin, and for aresident and later junior staff, I found my association withthese surgeons awesome.

After retirement, Babkin continued as Professor ofPhysiology until 1947, when he was invited by ProfessorWilder Penfield to continue his work as Fellow of theUniversity and Research Fellow at the McGill Department ofNeurology and Neurosurgery. It was in this laboratory that hewas the first to demonstrate, in experimental animals, therepresentation of several functions of the GI tract in thecerebral cortex. This work clarified the cortical inhibition ofgastric motility (8,11), cortical representation of feedingpattern (10) and, putting this together (11) with his very earlystudies in Pavlov’s laboratory on reflex regulation, he describedthe central location of the reflex connection of motility of thepylorus (12). Establishing the relationship of reflex responseand function of digestive organs and then demonstration oftheir cerebral location (8-12), Babkin was the first to establishthe main concepts of brain-gut-brain interaction.

WORLDWIDE APPRECIATION OF BABKIN’SCONTRIBUTIONS

Professor Babkin received many honours throughout his scien-tific career. In 1924, he was awarded a DSc at the University ofLondon, England. He received an honorary Doctorate of Lawfrom Dalhousie University in 1943. He was elected a Fellow ofthe Royal Society of Canada in 1930 and was President of itsBiological Sciences section between 1945 and 1946. He wasthe recipient of the Flavelle Medal of the Royal Society ofCanada in 1946. He was President of the CanadianPhysiological Society between 1944 and 1945. In the spring of1950, he was pleased to be elected a Fellow of the RoyalSociety of London and was prepared to be invested in England.Unfortunately, his death the same year took him away frompersonally receiving this honour. His appointment to Emeritus

Professor at McGill was announced posthumously. Dr Babkinremains greatly respected at McGill. His portrait hangs in thePhysiology Department, and its Chair, Dr Alvin Shrier,provided the picture of Dr Babkin to be included in thishistorical essay with pride and pleasure (Figure 1).

One of the honours that Canadian gastroenterologists andscientists in digestive diseases appreciate most is theFriedenwald Medal from the American GastroenterologicalAssociation (AGA) (Figure 8). Dr Julius Friedenwald was agastroenterologist on the staff of Johns Hopkins University inBaltimore, Maryland, USA. He held many teaching positionsand was a well-known author who published a number ofbooks and articles. He was President of the AGA. Dr Friedenwald died at the age of 75 years in 1941. In his hon-our, the AGA established a Medal for highest distinction inresearch in this field. This medal is presented at DigestiveDiseases Week (at the time of Babkin at the Annual Meetingof the American Gastroenterological Association), and thetext used for the presentation is published in a close subse-quent issue of Gastroenterology. The list of the yearly awardeesis a panorama of outstanding gastroenterologists and scientists(Table 1). Dr Babkin received this honor in 1949, and thespeech about him was given by his friend Dr Walter Alvarez(59). He described his personal friendship to Dr Babkin, andthen proceeded to talk about Dr Babkin’s devotion to hisstudents and theirs to him. He described some of the attributesI have seen, and his devotion interest to music and history. Hethen commented “Today, past 70, but still young in body andmental outlook, Dr Babkin is working away in Penfield’sNeurologic Institute at McGill. Still a student, he is anexample to all of us older men of how well a man can use theyears after his official retirement” (59).

Dr Babkin died during his sleep on a train the night of May 2, 1950 on his way back from Philadelphia to Montreal,where he was returning from the annual meeting of the AGAin Atlantic City, New Jersey, USA. His contributions to GIphysiology have been continued by his disciples, and althoughI was not his student, it was he who influenced me to take upthe field of GI physiology.



Figure 8) The Friedenwald Medal presented to Boris Babkin in 1949.This medal is the highest award of the American GastroenterologyAssociation

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CONCLUSION:WHAT DID BABKIN’S LIFE TEACH US?

“How can we know where we’re going if we don’t know wherewe are coming from? This question applies as much to nationsas it does to travellers, and it rings especially loudly in the earsof Canadians.” These are the first sentences of the cover of thebook Canada, A People’s History, by Gillmor and Turgeon. Thisquote and the following is most apt, because this country wasbuilt by “courageous explorers ... many of them exiles fromtheir homeland … who rose to the extraordinary challenge ofbuilding Canada” (60). Babkin’s life demonstrated in a mini-event what one could see of so many Canadians displayed onthe film production of the Canadian Broadcasting Corporationand its derivative book. Arriving with practically no English,writing his first papers in Russian (many of his Russian notesare still at the Osler Library at McGill), he learned English,worked hard, taught with excellence and, finally, broughthonour to Canada as the recipient of many great internationalawards. There are several lessons to be learned.

Canada has benefited from immigration of scientists andphysicians from all over the world. In gastroenterology, wehave seen giants like Hans Selye (stress ulcer – Hungary), John Brown (motilin and gastric inhibitory peptide – England),Charles Philippe Leblond (stem cell of the epithelium –France), Andrew Sass-Kortsak (Wilson’s disease – Hungary),

Aron Rappaport (hepatic physiological lobule – Bukovina:Austrian-Hungarian Monarchy) and many others. This intel-lectual exchange was beneficial for Canada and also interna-tionally, because many of their disciples went back to theirown country. One of the more disturbing events occurringsince the early 1990s was government’s acceptance of the rec-ommendations of the Barer and Stoddard (61) and theRomanow report (62), both of which suggested cutting downon employment of international graduates. Over the past 15 years, we have lost many outstanding investigators, whoafter obtaining research experience in Canada, left for theUnited States for clinical training, where many of themremained. Because of a shortage of physicians (63), the gov-ernment’s attitude has now been rethought and it now encour-ages the licensing of foreign graduates. However, it should bekept in mind that we do not only need clinicians but physicianscientists, specifically clinical investigators (1,64,65).

Babkin was trained as a physician, and although most of hiswork was as a basic scientist, his research questions were alwaysrelated to clinical problems. His work followed the process of aclinical investigator, to first evaluate the problem on the wholeanimal and if this did not provide an answer, to move to iso-lated organs, then to the cell and, finally, to subcellular events(1). For instance, to find the best approach to peptic ulcer sur-gery, it was necessary to know whether the antrum released agastric stimulant. Using isolated pouches, he demonstrated thephysiological presence of this stimulant (47). For chemicalproof, he invited Simon Komarov to isolate the physiologicalprinciple, an effort that took the latter several years (51-53).This extract led to the synthesis of gastrin by Tracy andGregory (66) many years after Babkin’s death. Every step wascarefully carried out by the investigators based on understand-ing and devising the method for each event.

Over the past decade, due to designing rapid-responseequipment, using mini quantities of material molecular biologyhas developed rapidly. Today, one can use machines that candetermine proteins, RNA, DNA and many other subcellularevents quickly. NanoDrop (www.nanodrop.com) advertises“1 µL drop samples, no cuvettes, 10-second measurement,broad spectral output” to measure nucleic acids and proteins.New England BioLabs (www.neb.com) advertises RheoSswitchfor “precise, variable control of mammalian gene expression”and eBioscience (www.ebioscience.com) provides “authentic”cytokines. The natural outcome of the availability of theseinstruments is to develop research that tends to concentrate onutilizing these techniques, often on isolated cells. This type ofresearch tends to remove itself from the kind of research thatmade the work of Babkin so remarkable. The time has come tofind a midway where clinical and pathophysiological researchand molecular biology meet. Fortunately, there are someCanadian clinical scientists who continue to fulfill this role.

Most of the obituaries of Babkin (13-15) and the presenta-tion of the Friedenwald Medal by Alvarez (59) acknowledgehis generosity to his coworkers and his devotion to facilitatetheir success. He never took credit for any of their work, thebest example being that, although rediscovery of gastrin couldnot have been achieved without him, Komarov published thisalone (51-53). Only when one reviews the story of gastrin doesone connect its development to Babkin. This unselfishdevotion is the example to follow, if scientists want to beremembered not only as great investigators, but also as teacherswho established their own school and contributed to societythrough their disciples.

Beck


TABLE 1Award recipients of the Julius Friedenwald medal

1941 Walter B Cannon

1942 Max Einhorn

1943 Thomas R Brown

1944 AJ Carlson

1945 Lewis Gregory Cole

1946 Frank H Lahey

1947 George B Eusterman

1948 Franklin W White

1949 Boris P Babkin

1950 BB Vincent Lyon

1951 Walter C Alvarez

1952 Sara M Jordan

1953 Burrill B Crohn

1954 Albert FR Andressen

1955 Frank Charles Mann

1956 Donald C Balfour

1957 T Grier Miller

1958 AH Aaron

1959 Russel S Boles, Sr

1960 Chester M Jones

1961 Jesse L Bollman

1962 Henry L Bockus

1963 Walter L Palmar

1964 Lester R Dragstedt

1965 Franklin Hollander

1966 Dwight L Wilbur

1967 J Arnold Bargen

1968 Julian M Ruffin

1969 Franz J Ingelfinger

1970 Andrew C Ivey

1971 Hans Popper

1972 J Earl Thomas

1973 Leon Schiff

1974 Charles F Code

1975 Joseph B Kirsner

1976 Thomas P Almy

1977 Charles J Best

1978 Morton I Grossman

1979 Hugh R Butt

1980 Horace W Davenport

1981 Wade Volwiler

1982 Thomas C Chalmers

1983 Gerald Klatskin

1984 Henry D Janowitz

1985 Kurt J Isselbacher

1986 Fred Kern, Jr

1987 Robert M Donaldson, Jr

1988 Frank P Brooks

1989 Marvin H Sleisenger

1990 Rudi Schmid

1991 Cyrus E Rubin

1992 Basil I Hirschowitz

1993 John S Fordtran

1994 Alan F Hofmann

1995 John T Farrar

1996 William Silen

1997 David H Alpers

1998 Eugene D Jacobson

1999 Jerry S Trier

2000 Howard M Spiro

2001 Don W Powell

2002 Sidney Cohen

2003 Tadataka Yamada

2004 Jon I Isenberg

2005 Ralph A Giannella

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Perhaps the most important lesson from Professor Babkin isthat he considered it a duty to publish mainly in Canadianjournals and was still able to attain international recognition(2,5,6,27-31,36,38,41,54,55,57,58). Canadian scientists oftoday have abandoned this responsibility to our journals. Tothe detriment of our Canadian journals, they send their bestpapers to foreign publications. When asked why, the answer isthat, to be successful in obtaining research grants from theMedical Research Council of Canada (MRC) and now, underits new name, the Canadian Institute of Health Research(CIHR), one has to publish internationally, because publishingin Canadian journals is considered of lesser value and lowerimpact. In Babkin’s time, research support was provided by theuniversities, and there was no need for competition for moneyuntil the MRC was established in 1960 (67). This attitude bythe MRC and CIHR committees to judge progress by thejournal of publication rather then its content leads to a self-destructive, vicious circle. If the best Canadian papers are notsubmitted to Canadian journals, our journals becomeweakened, and thus, has supported the above preconceivedidea. Could we have changed this perception? Most successfulinvestigators in gastroenterology are or were on MRC or CIHRcommittees, and some have attempted to initiate a change.However, in spite of numerous attempts to request a specialgastroenterology panel from the MRC (56) and from theCIHR (64,68,69), gastroenterology remains a part of theInstitute of Nutrition, Metabolism and Diabetes and its grantsare judged in the Experimental Medicine Committee. Thiscommittee judges submissions of five other specialties. Tochange this attitude, a consensus would have to be reachedwith scientists on the panel in other fields.

The problem of degrading publications in Canadian journals,however, is too important to be left to an agreement by singlecommittees. It needs an overall decision by the CIHR council.The reputation of Canadian research is not only its scientists,but the value of their home journal. The goal of the CIHR, likethat of Babkin’s, should be to support not only Canadianresearchers, but also our scientific journals. To achieve this (68),the CIHR council should insist that papers are assessed only ontheir scientific value and not where they were published. Thiswould result in submitting more Canadian papers to ourjournals, creating increasing competition for acceptance,gradually further improving their already high standard.

ACKNOWLEDGEMENTS: The author is grateful for theongoing support of the entire staff of the Bracken Health SciencesLibrary at Queen’s University, Kingston, Ontario, under thedirection of Suzanne Maranda. I would like to specially thankAnne B Smithers, Head of Technical & Document Services, andher staff for finding many of the references, and Darlene Lake, thelibrary’s document services coordinator, and her staff for obtainingthe many reprints quoted in this study. At McGill University inMontreal (Quebec), Pamela Miller, History of Medicine Librarianat the Osler Library, merits special thanks for providing guidanceof finding the data on Drs Babkin and Komarov. Also thanked areProfessor Dr Alvin Shrier, Chair of the Department of Physiologyfor providing a copy of Dr Babkin’s painting, and his secretary Ms Jay Bhat for her kind reception on my visit and for arrangingrephotographing of the exhibited old kymograph of theDepartment.



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3. Frommel E, Beck IT. L’association de quinidine et de phenobarbitaldans le traitment des affectiones cardiovasculaires. Praxis, RevueSuisse de Medicine 1948;46:1-2.

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8. Babkin BP, Speakman TJ. Cortical inhibition of gastric motility. J Neurophysiol 1950;13:55-63.

9. Babkin BP, Kite WC Jr. Gastric motor effects of acute removal ofcingulate gyrus and section of brain stem. J Neurophysiol1950;13:335-41.

10. Babkin BP, Van Buren JM. Mechanism and cortical representation ofthe feeding pattern. AMA Arch Neurol Psychiatry 1951;66:1-19.

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22. Bayliss W, Starling E. The mechanism of pancreatic secretion. J Physiol Lond 1902;28:325-52.

23. Modlin IM, Kidd M. Ernest Starling and the discovery of secretin. J Clin Gastroenterol 2001;32:187-92.

24. Modlin IM, Kidd M, Farhadi J. Bayliss and Starling and the nascenceof endocrinology. Regul Pept 2000;93:109-23.

25. Babkin BP. The influence of insulin on the formation of glycogen. BrJ Exp Pathol 1923;4:310-7.

26. Babkin BP, Starling EH. A method for the study of the perfusedpancreas. J Physiol 1926;61:245-7.

27. Babkin BP. The influence of natural chemical stimuli on themovements of the alimentary canal. Can Med Assoc J 1925;15:719-24.

28. Babkin BP, Alley A, Stavraky GW. Humoral transmission of chordatympany effect. Trans R Soc Can 1932;26:89-107.

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29. Feldberg W, Krayer O. Das Auftreten eines azetylcholinartigenStoffes im Herzvenenblut von Warmblutern bei Reizung der Nervivagi. Naunyn-Schmeidebergs Arch Exp Path Pharmak 1933;172:170-93.

30. Babkin BP. Antagonistic and synergistic phenomena in theautonomic nervous system. Trans R Soc Can 1946;40:1-25.

31. Babkin BP. The abnormal functioning of the gastric secretorymechanism as a possible factor in the pathogenesis of peptic ulcer.Can Med Assoc J 1938;38:421-9.

32. Soll AH. Potentiating interactions of gastric stimulants on [14 C]aminopyrine accumulation by isolated canine parietal cells.Gastroenterology 1982;83:216-23.

33. Sandor A, Kidd M, Lawton GP, Miu K, Tang LH, Modlin IM.Neurohormonal modulation of rat enterochromaffin-like cellhistamine secretion. Gastroenterology 1996;110:1084-92.

34. Kidd M, Tang LH, Miu K, Lawton GP, Sandor A, Modlin IM.Autoregulation of enterochromaffin-like cell histamine secretion viathe histamine 3 receptor subtype. Yale J Biol Med 1996;69:9-19.

35. Vineberg AM, Babkin BP. Histamine and pilocarpin in relation tothe gastric secretion. Am J Physiol 1931;97:69-73.

36. Babkin BP. The value of histamine as a test of gastric secretion from a physiological point of view. Can Med Assoc J 1930;23:268-72.

37. Babkin BP. Testing of the secretory activity of the gastric glands bymeans of histamine and insulin. Am J Dig Dis 1939;5:753-4.

38. Babkin BP, Schachter M. The chemical phase of gastric secretionand the surgery of the stomach. Mcgill Med J 1944;18:127-38.

39. Babkin BP, Hebb CO, Sergejeva MA. The parasympathetic likeeffect of splanchnic nerve stimulation on pancreatic secretion. Q J Exp Biol 1939;217-37.

40. Babkin BP. Blood sugar concentration and the external secretion ofthe pancreas. J Am Med Assoc 1935;105:1659-62.

41. Babkin BP. The mechanism of the secretory activity of the digestiveglands. Rev Can Biol 1943;2:416-34.

42. Edkins J. The chemical mechanism of gastric secretion. J Physiol1906;34:133-44.

43. Edkins JS. On the chemical mechanism of gastric secretion. Proc RSoc Lond B Biol Sci 1905;76:370-6.

44. Barger G, Dale H. The presence in ergot and physiological action ofB-imidazolelylethylamine. J Physiol 1910;40:38-40.

45. Sacks J, Ivy AC, Burgess JP, Vandolah JE. Histamine as the hormonefor gastric secretion. Am J Physiol 1932;101:331-8.

46. Schnedorf JG, Ivy AC. Failure of histamine and “Gastrin” toprovoke gastric secretion in monkeys with anacidity. Proc Soc ExperBiol Med 1937;36:192-3.

47. Babkin BP. The “chemical” phase of gastric secretion and itsregulation. Am J Dig Dis Nutr 1934;1:715-21.

48. Babkin BP. Modes of stimulation of the gastric secretion. Nature1934;134:1005.

49. Friedman MH. Dr. S. A. Komarov: 1892-1964. Gastroenterology1965;48:126-7.

50. Bralow SP. Special issue dedicated to S. A. Komarov. Am J Dig Dis1966;11:73-89.

51. Komarov SA. Gastrin. Proc Soc Exp Biol Med 1938;38:514-6.52. Komarov SA. Studies on gastrin. I. Method of isolation of a specific

gastric secretagogue from the pyloric mucous membrane and itsproperties. Rev Can Biol 1942;1:191-205.

53. Komarov SA. Studies on gastrin. II. Physiological properties of thespecific gastric secretagogue of the pyloric mucous membrane. Rev Can Biol 1942;1:377-401.

54. Babkin BP, Friedman MHF, MacKay-Sawyer ME. Vagal andsympathetic innervation of the snake. J Biol Bd Can 1934;1:239-50.

55. Babkin BP, Chaisson AF, Friedman MHF. Factors determining thecourse of the gastric secretion in Elasmobranchs. J Biol Bd Can1934;1:251-9.

56. Beck IT. History of the first 30 years of the Canadian Association ofGastroenterology. Can J Gastroenterol 1992;6:345-64.

57. Babkin BP, Webster DR. The regulation of bile flow through the bilepassages. Can Med Assoc J 1929;31:32-6.

58. Babkin BP, Armour JC, Webster DR. Restoration of the functionalcapacity of the stomach when deprived of its main arterial bloodsupply. Can Med Assoc J 1943;48:1-10.

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65. Beck IT, Depew WT. Canadian research fellowship training programsin digestive sciences: Achievements and challenges. Clin Invest Med 2001;24:44-53.

66. Tracy HJ, Gregory RA. Physiological properties of a series ofsynthetic peptides structurally related to gastrin I. Nature1964;204:935-8.

67. Romano T, Li A. Celebrating the Medical Research Council ofCanada. MR 21-19/2000, 1-24. 2000. Ottawa: Public Works andGovernment Services, 2000.

68. Fedorak RN. Economic impact of digestive, nutritional and oraldiseases in Canada. Can J Gastroenterol 2000;14:13-4.

69. Fedorak RN. Canadian Institutes of Health Research: Should therebe an institute for digestive sciences? Can J Gastroenterol1999;13:367-9.

Beck


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